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Epigenetic aging and PTSD outcomes in the immediate aftermath of trauma

Published online by Cambridge University Press:  23 March 2023

Anthony S. Zannas*
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Carolina Stress Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Sarah D. Linnstaedt
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Xinming An
Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Jennifer S. Stevens
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Nathaniel G. Harnett
Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA, USA
Alyssa R. Roeckner
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
Katelyn I. Oliver
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
David R. Rubinow
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Elisabeth B. Binder
Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
Karestan C. Koenen
Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA Department of Social and Behavioral Sciences, Harvard School of Public Health, Harvard University, Boston, MA, USA
Kerry J. Ressler
Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, MA, USA
Samuel A. McLean
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Anesthesiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Author for correspondence: Anthony S. Zannas, E-mail:



Psychological trauma exposure and posttraumatic stress disorder (PTSD) have been associated with advanced epigenetic age. However, whether epigenetic aging measured at the time of trauma predicts the subsequent development of PTSD outcomes is unknown. Moreover, the neural substrates underlying posttraumatic outcomes associated with epigenetic aging are unclear.


We examined a multi-ancestry cohort of women and men (n = 289) who presented to the emergency department (ED) after trauma. Blood DNA was collected at ED presentation, and EPIC DNA methylation arrays were used to assess four widely used metrics of epigenetic aging (HorvathAge, HannumAge, PhenoAge, and GrimAge). PTSD symptoms were evaluated longitudinally at the time of ED presentation and over the ensuing 6 months. Structural and functional neuroimaging was performed 2 weeks after trauma.


After covariate adjustment and correction for multiple comparisons, advanced ED GrimAge predicted increased risk for 6-month probable PTSD diagnosis. Secondary analyses suggested that the prediction of PTSD by GrimAge was driven by worse trajectories for intrusive memories and nightmares. Advanced ED GrimAge was also associated with reduced volume of the whole amygdala and specific amygdala subregions, including the cortico-amygdaloid transition and the cortical and accessory basal nuclei.


Our findings shed new light on the relation between biological aging and trauma-related phenotypes, suggesting that GrimAge measured at the time of trauma predicts PTSD trajectories and is associated with relevant brain alterations. Furthering these findings has the potential to enhance early prevention and treatment of posttraumatic psychiatric sequelae.

Original Article
Copyright © The Author(s), 2023. Published by Cambridge University Press

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